A porcine model of cystic fibrosis helps researchers study the disease.

In humans, cystic fibrosis clogs the airways of the lungs with mucus.

A new line of genetically altered piglets offers scientists a novel testing ground for the causes, progression, and treatments of cystic fibrosis. In the past, researchers relied on mice to study the disease, which in humans is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The mutation causes pancreatic failure, lung infections, and liver disease, among other problems. But mice with the flawed gene don't show humanlike symptoms of the disease, says HHMI investigator Michael J. Welsh.

“Mice just don't develop cystic fibrosis,” he says. “There are 20 theories as to why, but what it all comes down to is that if these animals don't get the symptoms, you can't use them to study the progression of the disease; you can't use them to test whether something treats the disease.”

So Welsh, at the University of Iowa, and collaborators turned to pigs—closer to human in terms of anatomy, physiology, biochemistry, size, lifespan, and genetics. They engineered pig cells with mutations in CFTR to make piglets with one bad copy of the gene, and then mated those pigs to produce offspring with both copies of CFTR mutated. These piglets show many of the hallmarks of human cystic fibrosis. The results appear in the September 26, 2008, issue of Science.

Affected humans and piglets are born healthy but develop increasing symptoms as they age. Having the pig model will allow researchers to study how cystic fibrosis progresses over time, says Welsh. “This is a disease that affects a whole organism and now we can study it in a whole organism.”

By comparing the affected pigs to mice with the same mutations, researchers may also be able to figure out why mice don't get symptoms of cystic fibrosis.

“We can look at what's different in mice and pigs that causes the mutation to have such different effects,” says Welsh. “Is it gene differences? Physiological differences? Anatomical? Maybe the answer will lead us to a therapy.”

Photo: CNRI / Photo Researchers, Inc.